Metalloproteinases and their roles in human cancer.

It is now widely appreciated that members of the matrix metalloproteinase (MMP) family of enzymes play a key role in cancer development and progression along with many of the hallmarks associated with them. The activity of these enzymes has been directly implicated in extracellular matrix remodeling, the processing of growth factors and receptors, the modulation of cell migration, proliferation, and invasion, the epithelial to mesenchymal transition, the regulation of immune responses, and the control of angiogenesis. Certain MMP family members have been validated as biomarkers of a variety of human cancers including those of the breast, brain, pancreas, prostate, ovary, and others.

Approaches to the discovery of non-invasive urinary biomarkers of prostate cancer.

Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. Prostate specific antigen (PSA) measured in blood has been used for decades as an aid for physicians to detect the presence of prostate cancer. However, the PSA test has limited sensitivity and specificity, leading to unnecessary biopsies, overdiagnosis and overtreatment of patients.

Mining the Human Proteome: Biomarker Discovery for Human Cancer and Metastases.

As our knowledge of the mechanisms underlying cancer development and progression has increased, so too have more effective, less toxic, and targeted therapies begun to reach the clinic. However, the full impact of these clinical advances and the practical success of the emerging field of precision medicine are dependent on the discovery and validation of sensitive and accurate biomarkers that can enable appropriate and rigorous sample type and patient selection, reliable longitudinal monitoring of therapeutic efficacy, and even risk assessment and early detection. Within the context of this review, we examine state-of-the-art approaches to the discovery and validation of noninvasive cancer biomarkers, with a specific emphasis on those that are protein or protein-associated ones.

Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer.

Background: The objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients.

Methods: Quantitative iTRAQ LC/LC/MS/MS analysis was used to identify proteins that are differentially expressed in the urine of men with BPH compared with those who have localized PCa. These proteins were validated in 173 urine samples from patients diagnosed with BPH (N = 83) and PCa (N = 90).

The mushroom Ganoderma lucidum suppresses breast-to-lung cancer metastasis through the inhibition of pro-invasive genes.

Breast cancer metastasis is one of the major reasons for the high morbidity and mortality of breast cancer patients. In spite of surgical interventions, chemotherapy, radiation therapy and targeted therapy, some patients are considering alternative therapies with herbal/natural products. In the present study, we evaluated a well-characterized extract from the medicinal mushroom Ganoderma lucidum (GLE) for its affects on tumor growth and breast-to-lung cancer metastasis.

Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.

Background: Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.

NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of breast cancer in vitro and in vivo.

Background: We have recently synthesized novel N-alkylated amino acid-derived hydroxamate, 2-[Benzyl-(2-nitro-benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N-propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHA against highly invasive human breast cancer cells MDA-MB-231 in vitro and in vivo.

Methodology/principal Findings: Cell growth was evaluated by MTT and soft agar assays.

Gossypol inhibits growth, invasiveness, and angiogenesis in human prostate cancer cells by modulating NF-κB/AP-1 dependent- and independent-signaling.

Although previous studies demonstrated anticancer activities of gossypol through the induction of apoptosis, the molecular mechanism(s) responsible for the inhibitory effects of gossypol on the metastatic behavior of cancer cells remain to be elucidated. Here, we show that gossypol inhibits growth of human prostate cancer cells through the modulation of cell cycle regulatory proteins. We also demonstrate that gossypol inhibits invasive behaviors (adhesion, migration, and invasion) and angiogenesis.

Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA.

Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231.

Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NF-κB and AP-1 signaling.

Background: Mushrooms are well recognized for their culinary properties as well as for their potency to enhance immune response. In the present study, we evaluated anti-inflammatory properties of an edible oyster mushroom (Pleurotus ostreatus) in vitro and in vivo.

Methods: RAW264.

Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages.

The multi-functional apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) DNA repair and redox signaling protein has been shown to have a role in cancer growth and survival, however, little has been investigated concerning its role in inflammation. In this study, an APE1 redox-specific inhibitor (E3330) was used in lypopolysaccharide (LPS)-stimulated macrophages (RAW264.7).

Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum, suppresses growth of colon cancer cells through ß-catenin signaling.

Colorectal cancer is one of the most common cancers in men and women in the world. Previous molecular studies have revealed that deregulation of the ß-catenin signaling pathway plays a crucial role in the progression of colorectal cancer. Therefore, modulation of the ß-catenin pathway offers a strategy to control colorectal cancer progression.

Suppression of proliferation and invasive behavior of human metastatic breast cancer cells by dietary supplement BreastDefend.

Aim: The study was to evaluate the effect of the dietary supplement BreastDefend (BD) on the proliferation and invasive behavior of highly metastatic human breast cancer cells in vitro.

Methods: Cell proliferation and cytotoxicity of BD was evaluated in MDA-MB-231 cells treated with BD (0-40 μg/mL) by MTT assay and trypan blue staining, respectively. Expression of cell cycle regulatory genes were determined by DNA-microarray analysis.

Pleurotus ostreatus inhibits colitis-related colon carcinogenesis in mice.

Colorectal cancer is one of the leading causes of cancer deaths in both men and women in the world. However, colon cancer can be prevented to some extent by consumption of edible natural products with chemopreventive properties. Therefore, we investigated, whether edible mushroom Pleurotus ostreatus (PO) has chemopreventive effect on inflammation-associated colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS).

Triterpenes from Ganoderma Lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK).

Medicinal mushroom Ganoderma lucidum is one of the most esteemed natural products that have been used in the traditional Chinese medicine. In this article, we demonstrate that G. lucidum triterpene extract (GLT) suppresses proliferation of human colon cancer cells HT-29 and inhibits tumor growth in a xenograft model of colon cancer.

Development of a new method for improved identification and relative quantification of unknown metabolites in complex samples: determination of a triterpenoid metabolic fingerprint for the in situ characterization of Ganoderma bioactive compounds.

Ganoderma lucidum is a mushroom with a long history of medical applications. Research has demonstrated chemotherapeutic effects of G. lucidum in tissue culture, and bioactive fractions of the mushroom have been shown to contain high levels of triterpenoids and polysaccharides.

Activated macrophages induce metastatic behavior of colon cancer cells.

Tumor-associated macrophages were linked to the growth, angiogenesis, and metastasis of variety of cancers. However, the role of macrophages in colon cancer is elusive. In the present study, we demonstrate that activated macrophage-conditioned medium (AMCM), containing tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6, markedly induced proliferation and migration of human colon cancer cells HCT116.

Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway.

In spite of the global consumption of mushrooms, only two epidemiological studies demonstrated an inverse correlation between mushroom intake and the risk of cancer. Therefore, in the present study we evaluated whether extracts from edible mushrooms Agaricus bisporus (portabella), Flammulina velutipes (enoki), Lentinula edodes (shiitake) and Pleurotus ostreatus (oyster) affect the growth of breast and colon cancer cells. Here, we identified as the most potent, P.

Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis.

Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B.

Inhibition activities of natural products on serine proteases.

Proteases play a key role in a variety of pathologies, including cancer, pancreatitis and thrombosis. Low molecular inhibitors can act as drugs to combat these pathologies. Twelve natural phenolic compounds and one alkaloid were evaluated.

Structural aspects of flavonoids as trypsin inhibitors.

In the search for new proteinase inhibitors we have focused on the screening and Computer Assisted Drug Design (CADD) studies of polyphenolic compounds. In this paper we report CADD of flavonoles and flavones as trypsin inhibitors concomitant by the screening results. 5,7-Dihydroxy flavonoid have been found to be a perspective trypsin/trypsin-like-enzyme inhibitor.